Understanding RNP remodelling uncovers RBPs functionally required for viral replication
Understanding RNP remodelling uncovers RBPs functionally required for viral replication
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DOI：
10.1101/350686
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发表时间：
2018-06
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通讯作者：
Manuel García-Moreno;M. Noerenberg;Shuai Ni;Aino I. Järvelin;Esther González-Almela;Caroline E. Lenz;Marcel Bach-Pages;V. Cox;R. Avolio;T. Davis;Svenja S. Hester;Thibault J. M. Sohier;Bingnan Li;M. A. Sanz;Luis Carrasco;Emiliano P. Ricci;V. Pelechano;Bernd Fischer;S. Mohammed;Alfredo Castello
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作者：
Manuel García-Moreno;M. Noerenberg;Shuai Ni;Aino I. Järvelin;Esther González-Almela;Caroline E. Lenz;Marcel Bach-Pages;V. Cox;R. Avolio;T. Davis;Svenja S. Hester;Thibault J. M. Sohier;Bingnan Li;M. A. Sanz;Luis Carrasco;Emiliano P. Ricci;V. Pelechano;Bernd Fischer;S. Mohammed;Alfredo Castello
RNA 结合蛋白 (RBPome) 的概要随着 RNA 相互作用组捕获 (RNA-IC) 的发展而得到了极大的扩展。然而，RBPome 的反应程度以及这些反应是否具有生物学相关性仍然未知。为了回答这些问题，我们创建了“比较 RNA-IC”来分析受到 RNA 病毒（称为 Sindbis (SINV)）攻击的细胞。引人注目的是，该病毒改变了 245 个 RBP 的活性，其中许多是 RNA-IC 新发现的。从机制上讲，SINV 感染后 RNA 结合的改变是由 RBP 的亚细胞定位和 RNA 可用性的变化引起的。此外，“RBPome”反应至关重要，因为动态 RBP 的扰动可以调节病毒感染细胞的能力。例如，XRN1 的消融会导致细胞难以感染，而 GEMIN5 则兼职作为一种新型抗病毒因子。因此，RBPome 重塑提供了一种机制，细胞可以通过该机制广泛地重新连接基因表达以响应生理信号。亮点 四分之一的 RBPome 在 SINV 感染后进行重塑。重塑是由蛋白质定位和 RNA 可用性的变化引起的。 RBPome 的重新布线对于病毒感染功效至关重要。我们发现 RBP 具有以前未知的抗病毒或促病毒活性。
The compendium of RNA-binding proteins (RBPome) has been greatly expanded by the development of RNA-interactome capture (RNA-IC). However, it remains unknown how responsive is the RBPome and whether these responses are biologically relevant. To answer these questions, we created ‘comparative RNA-IC’ to analyse cells challenged with an RNA virus, called sindbis (SINV). Strikingly, the virus altered the activity of 245 RBPs, many of which were newly discovered by RNA-IC. Mechanistically, alterations in RNA binding upon SINV infection are caused by changes in the subcellular localisation of RBPs and RNA availability. Moreover, ‘RBPome’ responses are crucial, as perturbation of dynamic RBPs modulates the capacity of the virus to infect the cell. For example, ablation of XRN1 causes cells to be refractory to infection, while GEMIN5 moonlights as a novel antiviral factor. Therefore, RBPome remodelling provides a mechanism by which cells can extensively rewire gene expression in response to physiological cues. HIGHLIGHTS A quarter of the RBPome remodels upon SINV infection. The remodelling is caused by changes in protein localisation and RNA availability. Rewiring of the RBPome is crucial for viral infection efficacy. We discover RBPs with previously unknown anti- or pro-viral activity.